rs746830945

Variant names:

• chr16-82068293-C-T
• rs746830945
• NM_002153.3:c.389C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002153.3(HSD17B2):​c.389C>T​(p.Pro130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P130P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: HSD17B2 NM_002153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.74
• Publications: 0 publications found

Genes affected

HSD17B2 (HGNC:5211): (hydroxysteroid 17-beta dehydrogenase 2) Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in response to retinoic acid. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B2-AS1 (HGNC:56281): (HSD17B2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15711814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.389C>T	p.Pro130Leu	missense	Exon 2 of 5	NP_002144.1	P37059

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.389C>T	p.Pro130Leu	missense	Exon 2 of 5	ENSP00000199936.4	P37059
	HSD17B2	ENST00000568090.5	TSL:3	c.-20C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000456529.1	H3BS44
	HSD17B2	ENST00000563491.5	TSL:3	c.-20C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000455992.1	H3BQY3

Frequencies

GnomAD3 genomes AF: 0.0000461 AC: 7 AN: 151946 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251374 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.0000349 AC: 51 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111996

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000461 AC: 7 AN: 151946 Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5 AN XY: 74186

African (AFR) AF: 0.0000725 AC: 3 AN: 41364

American (AMR) AF: 0.0000656 AC: 1 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00316 AC: 1 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.0
DANN	Benign	0.85
DEOGEN2	Uncertain	0.60	D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.7
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.20
Sift	Benign	0.26	T
Sift4G	Benign	0.22	T
Polyphen		0.27	B
Vest4		0.11
MutPred		0.47		Loss of disorder (P = 0.0626)
MVP		0.69
MPC		0.0055
ClinPred		0.089	T
GERP RS		-3.1
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.17
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs746830945; hg19: chr16-82101898; COSMIC: COSV99556899;